1. Field of the Invention
This invention relates to a pipette tip, which is obtained from molding of a plastic material and which is suitable for applying a predetermined amount of a liquid sample during chemical analyses. This invention particularly relates to a pipette tip, which is obtained from molding of a plastic material and which is suitable for applying a predetermined amount of an aqueous solution having a small surface tension and a high viscosity, particularly for applying a predetermined amount of a body fluid during clinical assays.
2. Description of the Prior Art
Recently, dry type clinical and chemical assays are carried out widely for easy and quick analyses. With the dry type clinical and chemical assays, droplets of liquid samples are independently applied to chemical analysis slides containing reagents which will react with specific constituents, such as glucose and urea nitrogen, in the liquid samples, such as blood. Changes in color, which are caused to occur by the reactions between the reagents and the specific constituents, are colorimetrically analyzed, and the amounts of the specific constituents in the liquid samples are thereby determined.
A droplet of a liquid sample has heretofore been applied to a chemical analysis slide with operations wherein a predetermined amount of the liquid sample is taken up into a pipette, a round droplet of the liquid sample is formed at the leading edge of the pipette, and the droplet is carefully applied to the center part of the chemical analysis slide.
During the analyses, in general, pipette tips formed of a plastic material are used. By way of example, a measured amount of a liquid sample falling within the range of 10 .mu.l to 120 .mu.l is taken up into a pipette tip, and a predetermined amount of the liquid sample falling within the range of several micro-liters to 100 .mu.l is fed out of the pipette tip. At this time, if the outer circumferential surface of the pipette tip is wet, part of the liquid sample will shift to the outer circumferential surface of the pipette tip. Such liquid shifting phenomenon will cause errors to occur in the results of analyses.
Disposable type pipette tips formed of plastic materials have heretofore been used widely in the physicochemical, medical, and biological fields. In most cases, aqueous solutions are processed with the disposable type pipette tips. The disposable type pipette tips are formed of plastic materials having good water repellency, such as polypropylene, polystyrene, and polyethylene. Therefore, when the disposable type pipette tip is used to process an ordinary aqueous solution, little solution will adhere to the outer circumferential surface of the pipette tip. However, if it occurs that a liquid remains on the outer circumferential surface of the pipette tip, during the feeding of a liquid sample out of the pipette tip, the liquid sample will be dragged to the outer circumferential surface of the pipette tip and will shift thereto.
The extent of adhesion of a liquid sample to the outer circumferential surface of a pipette tip and the extent of the liquid shifting to the outer circumferential surface depend largely on the surface tension and the viscosity of the liquid sample and the physical properties of the surface of the pipette tip.
For example, in cases where a polypropylene pipette tip is used which is designed to feed out a measured amount of a liquid sample falling within the range of 10 .mu.l to 100 .mu.l little liquid shifting phenomenon occurs with pure water, physiological saline, or the like.
However, blood plasma and blood serum, which are processed during clinical assays, have a high viscosity falling within the range of 1.5 to 2.5 cP. Therefore, the liquid shifting phenomenon easily occurs with such liquid samples. Also, whole blood samples have a viscosity as high as 10 cP to several tens of centipoises, and the liquid shifting phenomenon very easily occurs with such liquid samples.
FIG. 3A is an explanatory view showing how a droplet of a liquid sample is formed at the leading edge of a conventional pipette tip during the feeding of the liquid sample out of the pipette tip after the outer circumferential surface of the edge part of the pipette tip has been wiped with tissue paper, or the like. FIGS. 3B and 3C are explanatory views showing how a droplet of a liquid sample is formed at the leading edge of a conventional pipette tip during the feeding of the liquid sample out of the pipette tip without the outer circumferential surface of the edge part of the pipette tip being wiped. In FIGS. 3A, 3B, and 3C, reference numeral 1 indicates the edge part of the pipette tip, and reference numeral 2 indicates the leading edge of the pipette tip. Reference numeral 3 indicates the droplet of the liquid sample, and reference numeral 4 indicates the top layer of an analysis medium to which the liquid sample is to be applied.
As illustrated in FIG. 3A, when a liquid sample, which has been taken up into a pipette tip, is fed out, a spherical droplet should be formed under the leading edge of the pipette tip. In such cases, the sizes of the droplets become constant. Therefore, the liquid sample can be fed out reliably when the distance between the leading edge of the pipette tip and the sample receiving surface (for example, the surface of a liquid contained in a vessel, the surface of a wall of a device, such as a glass device, or the surface of spreading layer of a chemical analysis slide) is kept constant.
However, as illustrated in FIGS. 3B and 3C, if the liquid shifting phenomenon occurs, the droplet formed during the feeding of the liquid sample shifts upwardly. In such cases, the distance between the leading edge of the pipette tip and the bottom of the droplet thus formed becomes markedly smaller than the correct distance. Therefore, the droplet cannot reach the sample receiving surface, and cannot be applied thereto.
In cases where the liquid sample is applied manually, the position and the angle of the leading edge of the pipette tip can be found visually and can be adjusted in accordance with how the liquid sample is fed out. Therefore, the adverse effects of the liquid shifting of part of the liquid sample and the upward shifting of the droplet of the liquid sample can be eliminated. However, in cases where the liquid sample is applied automatically, the relationship between the position of the sample receiving surface and the position of the leading edge of the pipette tip is fixed. Therefore, if the upward shifting of the droplet of the liquid sample occurs, no liquid sample can be applied to the sample receiving surface.
Particularly, in the dry chemistry field, in order for a high analysis accuracy to be obtained, a droplet of a liquid sample must be formed as slowly as possible at the leading edge of a pipette tip. Thereafter, the droplet must be carefully applied to the surface of a chemical analysis slide. In such cases, serious problems will occur if the droplet of the liquid sample shifts upwardly.
In order to eliminate the problems described above, a method has been proposed wherein a surface sensor is used to detect the position of the sample receiving surface or a sensor is used to detect whether a normal droplet is or is not formed at the leading edge of a pipette tip.
Also, various attempts have heretofore been made to select the material and the shape of a pipette tip such that an aqueous solution sample may remove smoothly from the pipette tip, thereby to obtain a high accuracy of quantitative determination.
For example, a method has been proposed wherein a pipette tip is constituted of polypropylene, a silicone resin, or a fluorine resin. A method has also been proposed wherein only the leading edge of a pipette tip is made thin and short such that a droplet of a liquid sample does not easily shift upwardly. However, none of the proposed methods is suitable or satisfactory from the viewpoint of simplicity and the cost of the apparatus, and the effect on the prevention of the upward shifting phenomenon of a droplet of a liquid sample, particularly whole blood or blood plasma.
A liquid adhering to the edge part of a pipette tip may be wiped off each time a liquid sample is taken up into the pipette tip. With this method, the adverse effects of the liquid shifting phenomenon and the upward shifting phenomenon can be minimized. However, considerable time and labor are required to wipe the edge parts of pipette tips, and wiping failures will often occur. Also, even if an operator who carries out the wiping operation wear gloves during the wiping operation, there is the risk that he touches a blood sample, or the like, and is infected with a virus of hepatitis, or the like. Problems also occurs with regard to the discarding of wiping materials.